Circulating free DNA integrity and concentration as independent prognostic markers in metastatic breast cancer
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Circulating free DNA integrity and concentration as independent prognostic markers in metastatic breast cancer. / Cheng, Jie; Holland-Letz, Tim; Wallwiener, Markus; Surowy, Harald; Cuk, Katarina; Schott, Sarah; Trumpp, Andreas; Pantel, Klaus; Sohn, Christof; Schneeweiss, Andreas; Burwinkel, Barbara.
In: BREAST CANCER RES TR, Vol. 169, No. 1, 05.2018, p. 69-82.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Circulating free DNA integrity and concentration as independent prognostic markers in metastatic breast cancer
AU - Cheng, Jie
AU - Holland-Letz, Tim
AU - Wallwiener, Markus
AU - Surowy, Harald
AU - Cuk, Katarina
AU - Schott, Sarah
AU - Trumpp, Andreas
AU - Pantel, Klaus
AU - Sohn, Christof
AU - Schneeweiss, Andreas
AU - Burwinkel, Barbara
PY - 2018/5
Y1 - 2018/5
N2 - PURPOSE: Non-invasive blood-based molecular markers have been investigated for cancer diagnosis and prognosis. Circulating free or cell-free DNA (cfDNA) variables have been shown to be putative markers in breast cancer prognosis.METHODS: Here, we investigated the potential prognostic ability of cfDNA concentration and cfDNA integrity (cfDI) in a study cohort of 268 patients by quantitative PCR. We compared cfDNA concentration and cfDI at baseline and after one cycle of therapy in metastatic breast cancer (MBC) patients.RESULTS: A significantly increased cfDI (P = 1.21E-7 for ALU and P = 1.87E-3 for LINE1) and decreased cfDNA concentration (P = 1.17E-3 for ALU and P = 1.60E-2 for LINE1) in both repetitive DNA elements after one cycle of therapy was observed. A multiple Cox regression model indicated that cfDI and cfDNA concentration can serve as independent prognostic markers in patients at baseline with HR (95% CI) of 0.70 (0.48-1.01) for ALU cfDI, 0.63 (0.44-0.92) for LINE1 cfDI, 2.44 (1.68-3.53) for ALU cfDNA concentration, and 2.12 (1.47-3.06) for LINE1 cfDNA concentration and after one cycle of therapy with HR (95% CI) of 0.59 (0.42-0.84) for ALU cfDI, 0.51 (0.36-0.74) for LINE1 cfDI, 1.59 (1.31-1.92) for ALU cfDNA concentration, and 1.30 (1.17-1.45) for LINE1 cfDNA concentration, respectively. By comparing integrated prediction error of different models, cfDNA variables were shown to improve the prognostic power of the CTC status.CONCLUSIONS: We hereby show that cfDNA variables, especially in combination with other markers, can serve as attractive prognostic markers for MBC patients at baseline and during the systematic therapy.
AB - PURPOSE: Non-invasive blood-based molecular markers have been investigated for cancer diagnosis and prognosis. Circulating free or cell-free DNA (cfDNA) variables have been shown to be putative markers in breast cancer prognosis.METHODS: Here, we investigated the potential prognostic ability of cfDNA concentration and cfDNA integrity (cfDI) in a study cohort of 268 patients by quantitative PCR. We compared cfDNA concentration and cfDI at baseline and after one cycle of therapy in metastatic breast cancer (MBC) patients.RESULTS: A significantly increased cfDI (P = 1.21E-7 for ALU and P = 1.87E-3 for LINE1) and decreased cfDNA concentration (P = 1.17E-3 for ALU and P = 1.60E-2 for LINE1) in both repetitive DNA elements after one cycle of therapy was observed. A multiple Cox regression model indicated that cfDI and cfDNA concentration can serve as independent prognostic markers in patients at baseline with HR (95% CI) of 0.70 (0.48-1.01) for ALU cfDI, 0.63 (0.44-0.92) for LINE1 cfDI, 2.44 (1.68-3.53) for ALU cfDNA concentration, and 2.12 (1.47-3.06) for LINE1 cfDNA concentration and after one cycle of therapy with HR (95% CI) of 0.59 (0.42-0.84) for ALU cfDI, 0.51 (0.36-0.74) for LINE1 cfDI, 1.59 (1.31-1.92) for ALU cfDNA concentration, and 1.30 (1.17-1.45) for LINE1 cfDNA concentration, respectively. By comparing integrated prediction error of different models, cfDNA variables were shown to improve the prognostic power of the CTC status.CONCLUSIONS: We hereby show that cfDNA variables, especially in combination with other markers, can serve as attractive prognostic markers for MBC patients at baseline and during the systematic therapy.
KW - Journal Article
U2 - 10.1007/s10549-018-4666-5
DO - 10.1007/s10549-018-4666-5
M3 - SCORING: Journal article
C2 - 29340881
VL - 169
SP - 69
EP - 82
JO - BREAST CANCER RES TR
JF - BREAST CANCER RES TR
SN - 0167-6806
IS - 1
ER -